Parkinson's disease (PD) is characterized by slow and progressive degeneration of nigrostriatal dopaminergic neurons. A substantial body of evidence implicates roles for glutamate-mediated excitotoxicity and/or oxidative stress in the pathogenesis of this disease, however the mechanism(s) involved in the loss of these dopaminergic neurons remain unknown. One type of glutamate receptor that has gained recent interest as a potential therapeutic target is the metabotropic glutamate receptor (MGluR). These receptors have been shown previously to modulate neural injury in various experimental models; however, potential neuroprotective effects of mGluRs have not been examined closely in experimental models of PD. The experiments in this proposal will shed important insight into now only the localization of mGluRs on DA neurons but their potential involvement in MPP+-induced neuronal death. Furthermore, results from the proposed studies will lay the foundation for future in vivo studies in animal models of parkinsonism (e.g., MPTP-treated mouse or monkey). With the potential etiologic of excitotoxicity in PD, the involvement of mGluRs in MPP+-induced neuronal death is critical in understanding the possible role of these glutamate receptors in the pathology of this disease.